Tung-Ying Chao

Endobronchial Ultrasonography-Guided Transbronchial Needle Aspiration Increases the Diagnostic Yield of Peripheral Pulmonary Lesions: A Randomized Trial

BACKGROUND The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined. DESIGN A prospective, randomized trial. METHODS Two hundred two patients with PPLs and positive EBUS findings were enrolled. They were randomly classified into two groups. In the EBUS conventional diagnostic procedures (CDPs) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared. RESULTS A total of 182 patients (94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed. The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p < 0.001). Concerning the three different techniques, TBNA showed the highest diagnostic yield (62.5%) in comparison to TBB (48.9%) and to BW (19.8%). The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions (p = 0.89). No additional adverse effects were observed in the EBUS-TBNA plus CDPs group. CONCLUSIONS Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00626587.

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

BackgroundTo investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.MethodsA total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.ResultsWe newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).ConclusionsTLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.

Prognostic factors of tracheobronchial mucoepidermoid carcinoma--15 years experience.

Background and objectives:  Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patients prognosis and the tumours histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer.

Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Background Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS) and overall survival (OS) in EGFR-mutant patients with NSCLC. Materials and Methods Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR. Results The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001). Conclusion A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

Peripheral Immune Cell Gene Expression Changes in Advanced Non-Small Cell Lung Cancer Patients Treated with First Line Combination Chemotherapy

Introduction Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy. Methods To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment. Results Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality. Conclusions Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.

A cluster of patients with severe acute respiratory syndrome in a chest ward in southern Taiwan

ObjectiveSevere acute respiratory syndrome (SARS) is an emerging and easily clustering infectious disease. We describe an outbreak of SARS in a chest ward of a medical center in southern Taiwan and seek to identify the risk factors of those SARS patients who required mechanical ventilation. We focus on previous health patients.DesignThis retrospective case series was collected during the SARS outbreak. Degrees of severity were established, based on whether intubation and mechanical ventilation was necessary.SettingA 2500-bed medical center in southern Taiwan.PatientsForty-four patients exhibited symptoms that met the modified World Health Organization (WHO) definition of SARS. These included of three subgroups: health-care workers (n=16), relatives (n=14), and patients already admitted for other ailments (n=14). Of these, 20 eventually required mechanical ventilation.Measurements and resultsLaboratory analyses showed statistically significant differences between intubated and nonintubated patients in white blood cell count, neutrophil percentage, and C-reactive protein level as well as in age and underlying malignancy. Risk factors for SARS patients who had been healthy prior to their illness included old age, high peak fever grade, increased neutrophil count, increased neutrophil percentage, and close or prolonged contact with a SARS patient.ConclusionsOld age, high white blood cell counts, high peak grade fever, and close or prolonged contact with a SARS patient increase the risk of intubation in previous healthy SARS patients.

NEW IMAGE CHARACTERISTICS IN ENDOBRONCHIAL ULTRASONOGRAPHY FOR DIFFERENTIATING PERIPHERAL PULMONARY LESIONS

Endobronchial ultrasonography (EBUS) rapidly and accurately localizes peripheral pulmonary lesions. It can aid differential diagnosis by characterizing lesions and discriminating between neoplastic and non-neoplastic disease. From July 2005 through December 2006, patients with peripheral lesions underwent EBUS examination in a tertiary-referral teaching hospital. Image characteristics were subsequently correlated with definite histopathologic diagnosis. Three current-issued image patterns of EBUS were assayed from 40 initial patients, including (a) hypoechoic areas, (b) anechoic areas and (c) luminant areas around the probe. Excluding 22 cases because of inconsistent typing, 193 patients possessing definite diagnoses were enrolled in the investigation, of which 107 cases (55.4%) were neoplastic diseases. Hypoechoic areas appeared to be unrelated to the nature of the lesions (p = 0.288). Most lesions with anechoic areas were neoplasms (18 of 21 cases, 85.7%) and lesions without luminant areas suggested non-neoplastic disease (19 of 24 cases, 79.2%). Anechoic and luminant areas were significantly different between neoplasm and non-neoplasm groups (p = 0.003 and p < 0.001, respectively). The average additional time for EBUS required was 3.85 +/- 2.36 min (range 1 to 13 min). In conclusion, this uncomplicated and time-saving method of using EBUS image patterns could provide additional information to facilitate differential diagnoses.

Aberrant Toll-like receptor 2 promoter methylation in blood cells from patients with pulmonary tuberculosis

OBJECTIVES Toll-like receptor 2 (TLR2) is a major mediator of innate immunity against tuberculosis (TB). This study aimed to determine if TLR2 promoter DNA methylation is associated with pulmonary TB. METHODS The DNA methylation levels of 20 CpG sites over the TLR2 promoter region and TLR2 gene/protein expressions of immune cells of the blood were examined in 99 sputum culture-positive pulmonary TB patients and 77 healthy subjects (HS). RESULTS TB patients had higher methylation levels over five CpG sites (3, 7, 9, 13, and 18), lower TLR2 gene expression, lower TLR2 expression on monocyte, higher TLR2 expression on NK cell, and higher serum TNF-α/IFN-γ levels than HS after adjusting for confounding factors. Patients with a high bacillary load had lower methylation levels at CpG-15, -17, and -20. Patients with drug-resistant TB had higher CpG-18 methylation levels and lower TLR2 expression on NK cell. Patients with far advanced lesion on chest radiograph had higher serum TNF-α level and higher TLR2 expression on NK cell. Patients with a high TLR2 expression on NK cell had lower one-year survival. CpG-18 methylation level, TLR2 expressions on monocyte/NK cell, and TNF-α/IFN-γ levels were all reversed to normal after 6-month anti-TB treatment. CONCLUSIONS Aberrant methylation of certain CpG sites over TLR2 promoter region is associated with active pulmonary TB or its phenotypes, probably through the down-regulation of TLR2 expression.

First- or Second-line Gefitinib Therapy in Unknown Epidermal Growth Factor Receptor Mutants of Non-Small-Cell Lung Cancer Patients Treated in Taiwan

Gefitinib is effective in treating patients with non-small-cell lung cancer (NSCLC). The response rate and improvement in survival are related to several aspects, including race, gender, smoking status, and histology; however, little is known about the relationship between survival and length of gefitinib treatment. We conducted this retrospective study to examine this relationship and identify the predictive factors influencing survival and tumor response in chemonaive and chemotherapy patients who had stage IIIb or IV NSCLC with unknown epidermal growth factor receptor mutants. This analysis was aimed to clarify the difference between first- and second-line gefitinib therapy. Among the 918 newly diagnosed, inoperable NSCLC patients from March 2003 to December 2006, 437 (47.6%) had ever received gefitinib therapy. One hundred forty-nine patients (34.0%) who selected gefitinib as first- or second-line therapy were included in the analysis. The overall survival rates of first- and second-line gefitinib therapy were 12.8 months and 20.7 months, respectively (P = .110). The shorter overall survival may be caused by the omission of platinum-based doublet chemotherapy in 37 patients from the first-line group (39.4%). There was also no significant difference in progression-free survival (6.8 months versus 4.9 months; P = .415), and the objective tumor response and disease control rates were similar. Better prognosis and tumor response was associated with female gender, adenocarcinoma, nonsmokers, and good performance status. The difference in overall survival between patients undergoing second-line treatment compared with those undergoing first-line treatment preceding chemotherapy was significant (P = .041). The overall survival, progression-free survival, and tumor response rates were similar in the patients who received gefitinib as initial therapy or after conventional chemotherapy.

Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Background Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. Materials and Methods This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. Results Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. Conclusion Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.